The present invention relates generally to apparatus for gas chromatography, and more specifically to microfabricated gas chromatographic columns designed for effective packing with particulate chromatographic media.
Analysis of chemical samples has long been carried out using gas chromatography. Generally, gas chromatography involves separation of chemical species transported in a mobile gas phase in which the chemical species, called analytes, are volatized and carried along by the mobile phase. The mobile phase is forced through or past a stationary phase which is typically a polymer film or a porous film or particle.
The chemical species of interest will have different affinities for the stationary phase, as well as different vapor pressures (tendency to be in the vapor or mobile phase). As the mobile phase is forced through and/or past the stationary phase, the analytes are retained to different degrees in the stationary phase, resulting in different effective velocities through the column, the net result being separation of the chemical species in the sample.
In a common approach to gas chromatography, narrow tubes called columns are packed with a particulate stationary phase, through which the mobile phase is forced. A sample of the chemical species to be separated is typically injected into such a column along with a small amount of the mobile phase. Then the sample is transported through the column by continuous addition of pure mobile phase.
The average rate at which an analyte moves through is determined by the flow rate of the mobile phase, the affinity the analyte has with the stationary phase, and the vapor pressure of the analyte. When the analyte emerges from the column, the elution time is determined using a detector. This elution time provides considerable information about the nature of the analyte.
In some cases the detector simply signals the presence of some material in the eluent other than the mobile phase itself, while in other cases the detector provides additional information about the chemical makeup of the analyte (for example, when a portion of the eluent is directed into a mass spectrograph).
Many types of stationary phases are used in chromatographic analysis. These can have a variety of physicochemical properties, and can also take different physical forms. In the simplest form, the stationary phase is simply a solid or a collection of solid particles, and the analyte is adsorbed on the surface of the solid making up the stationary phase.
More commonly, though, the surface of the stationary phase material is altered to obtain a desired chemical affinity. This alteration can involve coating a solid support with a thin liquid phase, in which the analyte alternately is sorbed and released from the thin liquid phase as the mobile phase moves over the stationary phase. A stationary phase can be altered by covalently attaching molecules thereto which have a special affinity (or lack thereof) for certain chemical species of interest. Many other examples are known in the art.
Gas chromatographic columns are usually based upon open tubular columns or on tubular packed beds. Open tubular columns are typically about 0.1-0.5 millimeters in inside diameter and 5 to 30 meters in length, with a submicron polymer layer on the inside of the tube making up the stationary phase. Tubular packed beds are typically about 3 millimeters in inside diameter and 2-3 meters in length, and are filled with a solid powder whose porous surfaces or surface coating forms the stationary phase.
Gas chromatographic columns must have considerable length to provide adequate separation of analytes. However, there is a high cost to be paid in providing such long columns. Typically the column must be maintained at a constant and elevated temperature, which requires a large heated and insulated enclosure whose operation may require hundreds to thousands of watts for operation. Long columns are often fragile as well, which limits their potential utility.
There are many potential applications for chromatographic analysis which would greatly benefit from development and implementation of smaller and more thermally efficient chromatographic columns. Among these would be included process control, industrial hygiene, environmental analysis, portable chemical analysis equipment, first responder tools, point-of-care diagnostics, and many more. As a result, there is a long-felt need for chromatographic columns which provide a long column length within a small column footprint, volume, and power requirement.
There have been previous examples of miniature chromatographic columns built using microfabrication techniques based on silicon lithography similar to those used to fabricate LIGA and microelectromechanical systems (MEMS).
The prior art includes description of a microfabricated column for gas chromatography which comprises a high aspect ratio channel in the form of a spiral on a silicon substrate. When formed, the grooves are open at the surface of the silicon substrate. The grooves are coated with a thin polymer stationary phase, and then the channel is sealed by attaching a Pyrex cover to the surface of the silicon substrate.
This microfabricated gas chromatographic column is in function, if not in specific structure, a miniature version of the conventional open tubular column. Such columns are useful for separation of certain types of volatile and semivolatile analytes. However, the use of a thin polymer stationary phase combined with the relatively short length of the microfabricated column (roughly one meter compared to the conventional 5 to 30 meters) significantly limits the separation ability of this prior art microfabricated column, especially for analysis of gaseous mixtures.
There is thus a need for a miniature analog of the tubular packed bed gas chromatographic column. The use of a packed particulate stationary phase provides much larger surface area than is possible through use of a thin polymer stationary phase. In addition, the tortuous path which must be taken by the mobile phase through a packed particulate stationary phase in a tubular packed bed leads to more effective analyte separation in a given column length.
A new type of miniature packed gas chromatographic column has been invented. These columns are fabricated by sealing a cover plate onto a substrate whose surface is configured so as to form an elongated column comprising a packing retainer which serves to retain a particulate chromatographic medium within the column. These columns achieve effective and rapid analyte separation with a very small footprint and desirable thermal characteristics.